To report the outcomes of arthroscopic meniscectomy (AM) at 20 years of follow-up through timing/rate of conversion to total knee replacement (TKR) and Knee Injury and Osteoarthritis Outcome Score (KOOS), focusing on detection of specific predictor variables for these outcomes, in patients 50 to 70 years old. We performed a retrospective study of 289 patients, ages at surgery 50 to 70 years, with diagnosis of degenerative meniscal tear who underwent arthroscopic meniscectomy. We collected the following baseline data: age, sex, injured meniscus (medial, lateral, or both), knee alignment, osteoarthritis (OA), associated lesion identified during arthroscopy, and associated procedure performed during arthroscopy. At 20 years of follow-up, we collected rate and timing of TKR conversion, and we evaluated clinical outcomes with KOOS. Female sex (P < .01), older age (P < .01), lateral meniscectomy (P = .02), malalignment (P = .03), and advanced chondral lesion (P < .01) were found to be significantly related to subsequent TKR. No significant correlation was found between amount of resection and subsequent TKR (P = .26). Negative predictor factors to obtain equal or superior to age- and sex-adjusted KOOS scores were age 60 to 70 years at time of AM (P = .03) and lateral meniscectomy (P = .02). We report a 15.7% conversion rate at 20 years from AM to TKR and a mean time between surgeries of 7 years. Subsequent TKR in the 20 years after AM for degenerative meniscus tears were significantly associated with preoperative OA and chondral lesion (Kellgren Lawrence 2; Outerbridge >2), lateral meniscectomy, age at surgery, female sex, and malalignment. Furthermore, age >60 years, lateral meniscectomy, and concurrent anterior cruciate ligament reconstruction were negative predictors for poor clinical outcomes at 20 years. Therefore, if patients present with negative predictor factors, the AM should not be proposed as second-line treatment, and nonoperative management should be continued until TKR is unavoidable. IV, case series.