Although many studies have compared outcomes of laparoscopic appendectomy (LA) and open appendectomy (OA), some clinical and economic outcomes continue to be controversial, particularly in low-medium-income countries. We aimed at determining clinical and economic outcomes associated with LA versus OA in adult patients in Colombia. Retrospective, cohort study based on administrative healthcare records included all patients who underwent LA or OA in Colombia's contributory regime between July 1, 2013, and September 30, 2015. Outcomes were 30-day mortality rates, ICU admissions rates, length of stay (LOS), and hospital costs provided until discharge. Propensity score matching techniques were used to balance the baseline characteristics of patients (age, sex, comorbidities based on the Charlson index, insurer, and geographic location) and to estimate the average treatment effect (ATE) of LA as compared to OA over outcomes. A total of 65,625 subjects were included, 92.9% underwent OA and 7.1% LA. For the entire population, 30-day mortality was 0.74 per 100 appendectomies (95% CI 0.67-0.81), the mean and median LOS were 3.83 days and 1 day, respectively, and the ICU admissions rate during the first 30 days was 7.92% (95% CI 7.71-8.12). The ATE shows an absolute difference in the mortality rate after 30 days of -0.35 per 100 appendectomies (p = 0.023), in favor of LA. No effects on ICU admissions or LOS were identified. LA was found to increase costs by 514.13 USD on average, with total costs of 772.78 USD for OA and 1286.91 USD for LA (p < 0.001). In Colombia's contributory regime, LA is associated with lower 30-day mortality rate and higher hospital costs as compared to OA. No differences are found in ICU admissions or LOS.